1. Field of the Invention
The present invention relates to the use of an improved method of optimization of the settings and post-operative function of shunts used in hydrocephalus patients. Current methods and devices regarding shunting do not allow for real-time adjustment of cerebrospinal opening pressure of the specific patient in vivo. Shunts usually come in standard settings that can be adjusted after clinical assessment of the patient. The current invention allows for a real-time method to adjust shunt settings according to pressure and flow parameters of the specific patient in vivo, for initial shunt surgery, or for a shunt revision. Using this new method, the patient will be optimized in terms of real-time shunt settings, according to the patient's measured cerebrospinal pressure and flow information.
2. Description of the Related Art
Hydrocephalus is a condition affecting people who are unable to properly regulate their cerebrospinal fluid circulation. Cerebrospinal fluid (CSF) produced by the ventricular system is normally absorbed by the venous system. In a person suffering from hydrocephalus, the cerebrospinal fluid is not absorbed in this manner, but instead accumulates in the ventricles (free spaces) of the patient's brain. Normal pressure hydrocephalus (NPH) refers to a condition of pathologically enlarged ventricular size with normal pressures on lumbar puncture. If left untreated, an increasing volume of fluid can elevate the patient's intracranial pressure and can lead to serious medical conditions such as compression of the brain tissue and impaired blood flow to the brain.
The earliest description of hydrocephalus has been ascribed to Hippocrates (466-377 BC), who pointed out symptoms such as headache, vomiting and visual disturbance. Claudius Galen of Pergamon (130-200 AD) and medieval Arabian physicians also described hydrocephalus, believed to be due to an extracerebral accumulation of water.
Surgery to reduce fluid accumulation in the cerebrospinal fluid system was first performed by Le Cat in 1744, but it was not until the late nineteenth century, when sufficient pathophysiological knowledge and aseptic conditions were gained, that surgical procedures were truly introduced to treat hydrocephalus. In the 1960s, silicone and the invention of artificial valves led to a therapeutic breakthrough. With the development of an implantable shunt system to divert excess fluid, hydrocephalus went from being a fatal disease to becoming curable (Aschoff A, et al. Neurosurg Rev 22:67-93; discussion 94-5, 1999).
In 1965, Hakim and Adams described the newly discovered category of patients who also benefited from shunt surgery and who had normal cerebrospinal fluid pressure and benefited from shunt surgery (Hakim S and Adams R D. J Neurol Sci 2:307-27, 1965). The syndrome was named normal pressure hydrocephalus (NPH), and since then extensive work has been put into finding and developing new methods to identify those patients with NPH that will improve from shunt implantation surgery. Today, ventricular shunting is one of the most commonly performed neurosurgical procedures, including communicating and non-communicating hydrocephalus as well as shunt malformation. The annual incidence of operations varied between regional clinics from 2.3 to 6.3 per 100,000 inhabitants (Tisell M, et al. Acta Neurol Scand. 2005 August; 112(2):72-5.)
Shunting has dramatically changed the prognosis of people with hydrocephalus, many of them benefitting from normal life expectancies and regaining their baseline intelligence. The use of shunts, however, has created many unique problems of shunt dependence with frequent shunt revisions being the rule for most hydrocephalic patients. Shunt complications assume a major amount of all neurosurgeons' efforts.
CSF shunt implantation surgery involves establishing an accessory pathway for the flow of CSF in order to bypass an obstruction of the natural pathways. The shunt is positioned to enable the CSF to be drained from the cerebral ventricles or subarachnoid spaces into another absorption site, such as the right atrium of the heart or the peritoneal cavity, via a system of small tubes known as catheters. A regulatory device (known as a valve) can be inserted into the pathway of the catheters in order to regulate flow of CSF, depending on the pressure. This drainage enables the excess CSF within the brain to be evacuated and thereby, the pressure within the cranium to be reduced.
Valve mechanisms that continuously drain CSF are well known, as are valve mechanisms that control and/or adjust the opening pressure and/or drainage rate of the patient's CSF. However, currently available studies on determining what the optimal opening pressure of a hydrocephalus shunt should be are inconclusive. Earlier versions of the CSF shunt were fixed pressure shunts. The opening pressure of these shunts is fixed by the manufacturer, with three levels to choose from; a low pressure, medium pressure or high pressure valve. An example of such valves is the Hakim standard valves.
Today, in some hospitals the standard procedure is to start with a high opening pressure valve, and then adjust towards lower pressures if further improvement can be expected. In other hospitals the procedure is reversed. Thus the initial opening pressure chosen is low, and then increased if the patient experiences problems such as dizziness or other signs of over-drainage over time. The question of which shunt setting to start with was examined in a prospective Dutch study in 1998, comparing low versus high pressure shunt outcomes in 96 patients. Most differences in outcome between these two groups were statistically insignificant, even though the authors advised that patients with normal pressure hydrocephalus be treated with a low pressure shunt, (Boon A J et al. J. Neurosurg. 1998 March, 88(3):490-5).
When the adjustable shunt valve was introduced, such as the adjustable Codham Hakim programmable (CHP) valves, the possibility emerged of non-invasively adjusting and tailoring the opening valve pressure. A retrospective comparison of programmable shunt valves (CHP) vs. standard Hakim valves (H) was analyzed in 407 patients, to clarify whether CHP valves were advantageous compared to H valves, (Ringel F et al. Surg Neurol. 2005 January, 63(1):36-41.). Comparison was made with respect to valve-related shunt complications and surgical shunt revisions. The advantage implied with the Codham Hakim programmable valves did not translate into clinically significant findings, though the incidence of nontraumatic subdual hematomas and hygromas was higher in the CHP group. The authors therefore suggest it is still justified to implant standard Hakim valves in adult patients with hydrocephalus.
The studies mentioned above, on both fixed and adjustable valves, show that there is a need to be able to customize the opening pressure of a valve to the clinical needs of a patient who requires hydrocephalus surgery. One of the major issues in choosing valves is that there is no way of knowing what the actual opening pressure of a shunt will be once it is inserted into a patient. This is why the purpose of our invention herein is to use a postoperative CSF dynamical examination to determine the CSF dynamical state of the patient and CSF shunt in conjunction. Even if the in vitro settings of two shunts are the same, the resulting in vivo opening pressures will vary and depend on fluctuating individual conditions of the patients, such as differing abdominal pressure and compliance. By specific measurements and analyses, the actual resulting shunt opening pressure in vivo can be determined, and then adjusted according to a specific protocol to optimize shunt function. This can be accomplished by using our previously patented device for determining the hydrodynamics of the cerebrospinal fluid system, (WO 2006/091164).
The idea of the invention (WO 2006/091164) is to use the machine, which systematically generates or provides pressure and flow information, for determining with an uncertainty estimate, the hydrodynamic parameters of a patient in order to confirm diagnosis of hydrocephalus. The protocol can be based on a number of pressure-flow levels which are created by constant flow rates, flow rates that are varied according to a specific pattern, which generates a pressure fluctuation pattern, or adjustment of the flow while maintaining predetermined pressure levels. The machine can use predetermined time intervals for each pressure-flow level and automatically proceed to the next level when sufficient accumulated time with accepted data has been collected.
It is also possible to use signal analytic real-time methods, such as confidence intervals of a distribution, in order to estimate the accuracy or precision in the pressure and flow determined under each level and use this information to adaptively control when the examination shall proceed to the next pressure-flow level. Infusion is applied with cyclic variation in flow rate according to a predetermined pattern, superposed on one or more basic flow levels, and so, the response of pressure data is analyzed starting from or on the basis of a hydrodynamic model, with e.g. adaptive model-characterizing methods, such that values and the accuracy in estimated values for the patient's outflow resistance, resting pressure and compliance are continuously updated, whereupon the method is automatically proceeding to the next basic flow level when sufficient accuracy or precision has been obtained on one level.
Therefore, according to the invention herein, the dynamic information regarding the CSF pressure of the patient can also be gathered and interpreted as close to the patient's baseline, or resting pressure, when using the system described in (WO 2006/091164) or a similar system for measuring dynamic CSF pressure. The advantage this offers is that such dynamic information can, according to the invention herein, serve as a new method for real-time setting of the shunt pressure, as opposed to getting a static clinical picture of the patient and implanting a shunt that may not be optimal, even if it is adjustable. This would provide higher quality care to the patient, and reduce the cost of related healthcare.
A related patent, JP11299742A, can offer similar information regarding CSF pressure compared to WO 2006/091164. However, unlike the invention herein, this patent is based on resistance values against CSF absorption rather than continuous pressure measurements, and offers no method of dynamically measuring in vivo shunt opening pressure values. The method is manual and has no security connections between pump and pressure measurement and is therefore regarded as technically difficult to carry through as well as for final analysis. Drawbacks are that the precision of a determination based on two points as well as determination of a dynamic parameter in such a short time as 5 to 10 minutes is low and no statistic uncertainties are recorded.
Another method to set programmable shunts is described by Miyake et al (Neurol Med Chir (Tokyo) 48, 427-432, 2008). They use the patient's height and body-mass index to estimate the hydrostatic pressure and intraabdominal pressure giving an initial shunt setting. Another common technique used to clinically assess and guide shunt settings is the lumbar tap test. This is a relatively common test that can be done as an office procedure. Using lumbar puncture, 30 to 50 ml of CSF is removed with documentation of the patient's gait and cognitive function before and 30 to 60 minutes after the procedure. This is sometimes called the Fisher test. Common parameters measured before and after CSF removal includes measures of gait speed, stride length, reaction time, and tests of verbal memory and visual attention.
However, unlike the invention herein, those techniques do not measure resting CSF pressure, and do not allow for in vivo resulting shunt opening pressure to be determined.